Washout DNA copy number analysis by low-coverage whole genome sequencing for assessment of thyroid FNAs.

Background: Papillary thyroid microcarcinoma (PTMC) is defined as a papillary carcinoma measuring ≤ 10 mm. The current management of PTMC has become more conservative; however, there are high-risk tumor features that can be revealed only postoperatively. For thyroid cancer, BRAF mutations and somatic copy number variation (CNV) are the most common genetic events. Molecular testing may contribute to clinical decision-making by molecular risk stratification, for example predicting lymph node (LN) metastasis. Here, we build a risk stratification model based on molecular profiling of thyroid fine needle aspiration (FNA) washout DNA (wDNA) for the differential diagnosis of thyroid nodules. Methods: Fifty-eight patients were recruited, FNA wDNA samples were analyzed using CNV profiling through low-coverage whole genome sequencing (LC-WGS) and BRAF mutation was analyzed using quantitative PCR. FNA pathology was reported as a Bethesda System for Reporting Thyroid Cytopathology (BSRTC) score. Ultrasound examination produced a Thyroid Imaging Reporting and Data System (TIRADS) score. Results: In total, 37 (63.8%) patients with a TIRADS score of 4A, 13 (22.4%) patients with a TIRADS score of 4B, and 8 (13.8%) patients with a TIRADS score of 4C were recruited after ultrasound examination. All patients underwent FNA with wDNA profiling. CNVs were identified in 17 (29.3%) patients. CNVs were frequent in patients with a BSRTC score of V or VI, including eight (47.1%) patients with a score of VI and five (29.4%) with a score of V, but not in patients with a score of III, II, or I (0%). BRAF mutation was not significantly correlated with BSRTC score. LN metastasis was found more frequently in CNV-positive (CNV+) than in CNV-negative (CNV-) patients (85.7% vs. 34.6%, odds ratio = 11.33, p = 0.002). In total, three molecular subtypes of thyroid nodules were identified in this study: 1) CNV+, 2) CNV- and BRAF positive (BRAF+), and 3) CNV- and BRAF negative (BRAF-). For the CNV+ subtype, 10 (83.3%) lesions with LN metastasis were found, including four (100%) small lesions (i.e. ≤ 5 mm). For the CNV- and BRAF+ nodules, LN metastases were detected in only seven (60.0%) larger tumors (i.e. > 5 mm). For CNV- and BRAF- tumors, LN metastasis was also frequently found in larger tumors only. Conclusions: It is feasible to identify high-risk LN metastasis thyroid cancer from FNA washout samples preoperatively using wDNA CNV profiling using LC-WGS.

Objective Assessment of Hyposmia in Alzheimer's Disease From Image and Behavior by Combining Pleasant Odor With Unpleasant Odor.

Background: Olfactory functional magnetic resonance imaging (fMRI) of responses to a pleasant odor (PO) (lavender) can objectively evaluate olfactory dysfunction in Alzheimer's disease (AD) patients. The brain responses to a PO and unpleasant odor (UPO) were shown to differ in normal young people. Whether AD patients with olfactory dysfunction have the same brain response is not yet known. Objective: Our aim was to explore whether olfactory fMRI with both a PO and UPO can provide more information regarding olfactory impairment in AD than a PO alone. Methods: Twenty-five normal controls (NC), 26 individuals with mild cognitive impairment (MCI), and 22 AD patients underwent olfactory fMRI with lavender and pyridine odorants at three concentrations (0.10, 0.33, and 1.00%) with a 3.0-T MRI scanner. Results: There were no differences in the number of activated voxels in the primary olfactory cortex (POC) between PO and UPO conditions in the NC, MCI, and AD groups (SPM, paired t-test, uncorrected p < 0.001, extent threshold = 70). In the right inferior frontal gyrus, orbital part (F3O), the number of activated voxels was greater with the UPO than with the PO in the NC group (SPM, paired t-test, uncorrected p < 0.001, extent threshold = 70), but there were no differences in the MCI and AD groups. Regardless of PO or UPO conditions, there were significant differences in the number of activated voxels in the POC among the NC, MCI, and AD groups. With increasing odor concentration, the number of activated voxels in the POC decreased in the NC group but increased in the AD group. When 0.10% UPO was presented, the NC group (21/25) showed a lower breathing amplitude and shorter inhalation time, whereas the AD patients (0/22) did not show such changes in breathing. Conclusions: After PO and UPO inhalation, brain activation and respiratory behavior in AD patients were significantly different than in NC patients. Therefore, olfactory fMRI using both PO and UPO stimulation, compared with PO stimulation only, can provide more objective information regarding hyposmia associated with AD based on imaging and behavior.

The Profile of Secondary Glaucoma in China: A Study of Over 10,000 Patients.

BACKGROUND: Few studies have investigated the epidemiology of secondary glaucoma (SG) in China. This study analyzed the current profile of admitted patients with SG at the largest ophthalmic center in China. METHODS: SG cases were retrieved retrospectively by International Classification of Disease-10 clinical coding data from January 2010 to December 2019. Demographic data, etiologies, and the management of SG were analyzed. The ratios of the etiologies were compared with previously reported data from other regions. The etiologies and management between the 2010 to 2014 group and the 2015 to 2019 group were compared. RESULTS: A total of 11,730 cases were enrolled. The mean age of the patients with SG was 44.45±19.45 years old. Men (66.94%) were more vulnerable than women (33.06%). The etiologies of SG in 2010 to 2019 were trauma (28%), vascular disease (18%), lens-induced (9%), inflammation (11%), drug-induced (2%), anterior segment surgery (7%), posterior segment surgery (11%), syndrome-associated (4%), and tumors (1%). Compared with other regions, our data have a higher proportion of trauma and vascular disease-associated SG. Compared with 2010 to 2014, trauma-induced SG declined, and drug-induced SG, anterior segment surgery, and syndrome-associated SG increased in 2015 to 2019 (P<0.001). Vascular disease-associated SG cases were older than trauma-induced SCs and had a higher percentage in retired patients (P<0.001), whereas trauma-induced SGs were more prevalent in pediatric patients than vascular disease-related SGs (P<0.001). In addition, the application of drainage device implantation, cataract surgery, and cyclophotocoagulation increased, whereas trabeculectomy and anterior chamber paracentesis and cyclocryotherapy decreased in 2015 to 2019 (P<0.005). CONCLUSION: Although the etiology spectrum has changed during the last 10 years, trauma and vascular disease are still common causes of SG in southern China. Traditional antiglaucoma surgery decreased gradually, and more advanced treatments emerged for its treatment. Up-to-date knowledge of SGs reflects the impact of economic development and ophthalmic service improvement on SGs and is of great value for ophthalmologists to detect SGs early and manage them in a timely manner.

Caregiver burden, sleep quality, depression, and anxiety in dementia caregivers: a comparison of frontotemporal lobar degeneration, dementia with Lewy bodies, and Alzheimer's disease.

ABSTRACTBackground:Very few recent studies are available that compare caregiver burden, sleep quality, and stress in caregivers of different types of dementia. We aimed to investigate caregiver burden, sleep quality, and stress in caregivers of patients with frontotemporal lobar degeneration and dementia with Lewy bodies, as compared with caregivers of patients with Alzheimer's disease. METHODS: This study was carried out from March 2011 to January 2014. In total, 492 dyads of patient and caregiver (frontotemporal lobar degeneration, n = 131; dementia with Lewy bodies, n = 36; Alzheimer's disease, n = 325) participated in this study. We compared patients with respect to the Neuropsychiatric Inventory and caregivers with respect to the Zarit Caregiver Burden Interview, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, and Generalized Anxiety Disorder scale. RESULTS: Frontotemporal lobar degeneration and dementia with Lewy bodies patients presented significantly more neuropsychiatric symptoms compared to Alzheimer's disease patients. Caregivers of frontotemporal lobar degeneration and dementia with Lewy bodies patients experienced significantly more burden compared to Alzheimer's disease caregivers. Furthermore, among caregivers of both frontotemporal lobar degeneration and dementia with Lewy bodies patients burden was predicted by the neuropsychiatric symptoms, PHQ-9 scores, and GAD-7 scores. CONCLUSIONS: The frequency and severity of behavioral disturbances in patient and caregiver stress accounted for the increased caregiver burden, which suggests that frontotemporal lobar degeneration and dementia with Lewy bodies caregivers should receive more support than is currently available.